Suryana Eurwin, Jones Nicole M
Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW 2052, Australia.
Int J Dev Neurosci. 2014 Oct;37:69-75. doi: 10.1016/j.ijdevneu.2014.06.007. Epub 2014 Jul 4.
Myelination is an essential process in human development that is carried out by oligodendrocytes in the central nervous system. Hypoxic-ischaemic (HI) brain injury can disrupt myelination by causing oxidative stress, inflammation and excitotoxicity, resulting in the loss of myelin as well as cells of the oligodendrocyte lineage. We have previously shown that hypoxic preconditioning (HP) can protect against HI injury, however, to date there have been no reports of its effects on white matter injury. Sprague-Dawley rat pups (postnatal day (P) 6) were placed into control and HP groups. On P7, pups were further separated into HI and sham surgery groups. HI pups underwent a unilateral common carotid artery occlusion and then exposed to 8% oxygen for 3h. Sham pups underwent the same procedure without occlusion and were maintained in room air. Brains were removed 5 days post-surgery for analysis. In HI-only pups there was a significant reduction in brain volume observed. Consequently, when HP was performed prior to HI, the loss of brain tissue was prevented. The number of early and late oligodendrocyte progenitors (preOLs) in the corpus callosum was unaffected by HI, however, HI reduced the amount of myelin basic protein, indicating that HI may inhibit the maturation of preOLs. Whilst HP did not affect preOL density, it was found to prevent the loss of myelin caused by HI. This indicates that HP may either protect myelin directly or possibly promote the maturation of preOLs to regenerate the lost or damaged myelin.
髓鞘形成是人类发育过程中的一个重要过程，由中枢神经系统中的少突胶质细胞执行。缺氧缺血性（HI）脑损伤可通过引起氧化应激、炎症和兴奋性毒性来破坏髓鞘形成，导致髓鞘以及少突胶质细胞谱系细胞的丢失。我们之前已经表明，缺氧预处理（HP）可以预防HI损伤，然而，迄今为止，尚无关于其对白质损伤影响的报道。将Sprague-Dawley大鼠幼崽（出生后第6天）分为对照组和HP组。在出生后第7天，将幼崽进一步分为HI组和假手术组。HI组幼崽进行单侧颈总动脉闭塞，然后暴露于8%氧气中3小时。假手术组幼崽进行相同的操作但不进行闭塞，并置于室内空气中。术后5天取出大脑进行分析。在仅HI组的幼崽中，观察到脑体积显著减小。因此，在HI之前进行HP时，可以防止脑组织的丢失。胼胝体中早期和晚期少突胶质前体细胞（preOLs）的数量不受HI影响，然而，HI减少了髓鞘碱性蛋白的量，表明HI可能抑制preOLs的成熟。虽然HP不影响preOL密度，但发现它可以防止HI引起的髓鞘丢失。这表明HP可能直接保护髓鞘，或者可能促进preOLs的成熟以再生丢失或受损的髓鞘。
